Mutagenetix > Incidental Mutation

Incidental Mutation 'R0481:Hadhb'

43354

Institutional Source

Beutler Lab

Gene Symbol

Hadhb

Ensembl Gene

ENSMUSG00000059447

Gene Name

hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta

Synonyms

Mtpb, 4930479F15Rik

MMRRC Submission

038681-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.791) question?

Stock #

R0481 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

30360251-30389591 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 30373543 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 78 (H78Q)

Ref Sequence

ENSEMBL: ENSMUSP00000118296 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000026841] [ENSMUST00000114783] [ENSMUST00000114786] [ENSMUST00000123980] [ENSMUST00000197109]

AlphaFold

Q99JY0

Predicted Effect

probably damaging
Transcript: ENSMUST00000026841
AA Change: H78Q

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000026841
Gene: ENSMUSG00000059447
AA Change: H78Q

Domain	Start	End	E-Value	Type
Pfam:Thiolase_N	52	325	4.6e-96	PFAM
Pfam:ketoacyl-synt	86	193	1.8e-10	PFAM
Pfam:Thiolase_C	332	472	1.5e-51	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000114783
AA Change: H78Q

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000110431
Gene: ENSMUSG00000059447
AA Change: H78Q

Domain	Start	End	E-Value	Type
Pfam:Thiolase_N	55	325	1.4e-90	PFAM
Pfam:ketoacyl-synt	90	194	1.4e-10	PFAM
Pfam:Thiolase_C	332	472	1.3e-51	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000114786
AA Change: H78Q

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000110434
Gene: ENSMUSG00000059447
AA Change: H78Q

Domain	Start	End	E-Value	Type
Pfam:Thiolase_N	52	325	4.6e-96	PFAM
Pfam:ketoacyl-synt	86	193	1.8e-10	PFAM
Pfam:Thiolase_C	332	472	1.5e-51	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000123980
AA Change: H78Q

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000118296
Gene: ENSMUSG00000059447
AA Change: H78Q

Domain	Start	End	E-Value	Type
Pfam:Thiolase_N	52	129	3.7e-20	PFAM
Pfam:Thiolase_N	119	173	3.3e-17	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000127364

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000157488

Predicted Effect

probably benign
Transcript: ENSMUST00000197109

Meta Mutation Damage Score

0.3234

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.5%
20x: 93.3%

Validation Efficiency

95% (89/94)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the beta subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the beta subunit catalyzing the 3-ketoacyl-CoA thiolase activity. The encoded protein can also bind RNA and decreases the stability of some mRNAs. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation. Mutations in this gene result in trifunctional protein deficiency. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
PHENOTYPE: Mice homozygous for an ENU-induced mutation display reduced postnatal weight gain, multifocal cardiac fibrosis and hepatic steatosis, and develop cardiac arrhythmias that range from a prolonged PR interval to complete atrioventricular dissociation and lead to sudden between 9 and 16 months of age. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcg4	T	A	9: 44,190,666 (GRCm39)	N39Y	probably benign	Het
Adamts10	C	T	17: 33,768,347 (GRCm39)	Q840*	probably null	Het
Aff2	C	T	X: 68,878,248 (GRCm39)	T678I	probably damaging	Het
Ahctf1	A	G	1: 179,587,836 (GRCm39)	V1418A	probably benign	Het
Ankrd11	G	A	8: 123,626,775 (GRCm39)	R136C	probably damaging	Het
Arf5	A	G	6: 28,426,075 (GRCm39)	Y154C	probably damaging	Het
AW551984	A	G	9: 39,511,912 (GRCm39)	V33A	probably null	Het
B4galt5	A	G	2: 167,151,154 (GRCm39)	L118P	probably damaging	Het
Bcl9l	A	G	9: 44,417,979 (GRCm39)	I606V	probably benign	Het
Bdp1	A	G	13: 100,177,962 (GRCm39)	I1969T	probably benign	Het
Bicd1	A	T	6: 149,413,389 (GRCm39)	D260V	possibly damaging	Het
Cap1	A	T	4: 122,756,868 (GRCm39)	H272Q	possibly damaging	Het
Ccnk	A	G	12: 108,165,568 (GRCm39)		probably benign	Het
Cd209f	A	T	8: 4,155,558 (GRCm39)		probably null	Het
Cdk13	C	A	13: 17,894,079 (GRCm39)	A1123S	probably damaging	Het
Cdx1	C	T	18: 61,153,564 (GRCm39)	R158H	probably damaging	Het
Chd8	A	G	14: 52,474,663 (GRCm39)	S123P	probably benign	Het
Cwc22	G	A	2: 77,738,455 (GRCm39)	A497V	probably damaging	Het
Cwh43	T	C	5: 73,575,370 (GRCm39)	S296P	probably damaging	Het
Dhx38	A	T	8: 110,282,848 (GRCm39)		probably benign	Het
Dnah5	T	A	15: 28,383,745 (GRCm39)	M2989K	probably benign	Het
Dpy19l4	A	C	4: 11,272,993 (GRCm39)		probably benign	Het
F11r	A	T	1: 171,288,847 (GRCm39)	H155L	probably benign	Het
Fcgbpl1	A	T	7: 27,853,174 (GRCm39)	D1487V	probably damaging	Het
Fitm2	A	G	2: 163,311,634 (GRCm39)	V193A	probably benign	Het
Foxk1	T	A	5: 142,434,578 (GRCm39)	S281T	probably benign	Het
Furin	A	G	7: 80,043,297 (GRCm39)	C305R	probably damaging	Het
Fut8	T	A	12: 77,495,334 (GRCm39)	V308D	probably damaging	Het
Gjb3	T	A	4: 127,220,125 (GRCm39)	I136F	probably benign	Het
Glmn	A	T	5: 107,708,800 (GRCm39)	S385T	probably benign	Het
Glp1r	T	A	17: 31,150,191 (GRCm39)	M371K	probably benign	Het
Gpr179	T	C	11: 97,240,544 (GRCm39)	H293R	probably damaging	Het
H2-M11	A	T	17: 36,859,846 (GRCm39)	R280*	probably null	Het
Hectd4	A	G	5: 121,433,569 (GRCm39)		probably benign	Het
Hexa	A	G	9: 59,462,693 (GRCm39)		probably benign	Het
Hsh2d	G	A	8: 72,954,304 (GRCm39)	D229N	probably benign	Het
Hyal6	G	A	6: 24,743,417 (GRCm39)	C371Y	probably damaging	Het
Il1rap	T	C	16: 26,511,585 (GRCm39)	Y210H	probably damaging	Het
Ino80	A	T	2: 119,261,497 (GRCm39)	H722Q	probably damaging	Het
Kcnt1	A	G	2: 25,782,508 (GRCm39)	N200S	probably damaging	Het
Kif27	T	A	13: 58,459,078 (GRCm39)		probably benign	Het
Lyst	T	C	13: 13,852,537 (GRCm39)	V2179A	probably benign	Het
Macf1	C	A	4: 123,377,815 (GRCm39)		probably null	Het
Mamdc4	A	G	2: 25,461,228 (GRCm39)	M1T	probably null	Het
Mansc4	A	G	6: 146,976,725 (GRCm39)	I297T	possibly damaging	Het
Mdn1	G	A	4: 32,767,182 (GRCm39)		probably benign	Het
Mib2	A	G	4: 155,740,519 (GRCm39)		probably benign	Het
Mon2	A	G	10: 122,849,301 (GRCm39)	V1333A	possibly damaging	Het
Ndst2	T	C	14: 20,774,536 (GRCm39)	D840G	possibly damaging	Het
Nell2	A	T	15: 95,330,563 (GRCm39)		probably null	Het
Or4c102	A	T	2: 88,422,999 (GRCm39)	I284F	probably damaging	Het
Or4k51	T	A	2: 111,584,930 (GRCm39)	M112K	probably damaging	Het
Or5g29	C	A	2: 85,421,448 (GRCm39)	A188E	possibly damaging	Het
Pde5a	C	T	3: 122,611,726 (GRCm39)		probably benign	Het
Phip	A	G	9: 82,758,769 (GRCm39)		probably benign	Het
Polr2b	A	G	5: 77,479,929 (GRCm39)	I561V	possibly damaging	Het
Ppp4r3c2	T	C	X: 88,796,299 (GRCm39)	S44P	probably damaging	Het
Prkg2	A	T	5: 99,142,514 (GRCm39)		probably null	Het
Prl8a6	T	C	13: 27,617,084 (GRCm39)	D201G	probably benign	Het
Ptk6	G	A	2: 180,844,320 (GRCm39)		probably benign	Het
Ptprn2	T	C	12: 117,175,466 (GRCm39)		probably benign	Het
Rdh1	G	T	10: 127,598,993 (GRCm39)	R158L	probably damaging	Het
Rhbdl3	T	C	11: 80,214,175 (GRCm39)		probably benign	Het
Rims4	A	T	2: 163,706,040 (GRCm39)	V198E	probably damaging	Het
Ripk1	T	C	13: 34,193,733 (GRCm39)	S32P	probably damaging	Het
Rnf13	T	A	3: 57,686,872 (GRCm39)	N88K	probably damaging	Het
Rnf13	C	A	3: 57,714,474 (GRCm39)	L178I	probably damaging	Het
Slc17a5	G	T	9: 78,445,584 (GRCm39)		probably null	Het
Sorcs1	A	G	19: 50,624,891 (GRCm39)		probably benign	Het
Spata31e3	T	A	13: 50,401,000 (GRCm39)	Q442L	probably benign	Het
Srpk1	G	A	17: 28,809,218 (GRCm39)		probably benign	Het
Stk10	A	G	11: 32,564,708 (GRCm39)	K840E	probably damaging	Het
Suco	A	G	1: 161,689,882 (GRCm39)		probably benign	Het
T2	G	A	17: 8,636,007 (GRCm39)		probably null	Het
Tbc1d5	A	G	17: 51,226,079 (GRCm39)	S255P	probably damaging	Het
Tenm1	T	C	X: 41,625,058 (GRCm39)	Y2254C	probably damaging	Het
Tex9	T	A	9: 72,385,678 (GRCm39)	K11*	probably null	Het
Tlr4	A	G	4: 66,746,153 (GRCm39)	I29V	probably benign	Het
Tmem255a	A	T	X: 37,288,523 (GRCm39)	V278D	probably damaging	Het
Trpc3	T	C	3: 36,678,566 (GRCm39)	I840V	probably benign	Het
Trpm3	G	A	19: 22,878,435 (GRCm39)	R622Q	possibly damaging	Het
Vmn1r214	T	A	13: 23,219,464 (GRCm39)	Y319*	probably null	Het
Vmn1r53	A	T	6: 90,200,700 (GRCm39)	V208E	probably damaging	Het
Vmn2r89	T	C	14: 51,693,577 (GRCm39)	F309S	probably damaging	Het
Xirp2	T	A	2: 67,340,253 (GRCm39)	F831L	possibly damaging	Het
Yes1	G	T	5: 32,797,749 (GRCm39)	E23*	probably null	Het
Zfp292	A	T	4: 34,810,059 (GRCm39)	M995K	probably benign	Het

Other mutations in Hadhb

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02306:Hadhb	APN	5	30,371,747 (GRCm39)	missense	probably null	0.99
IGL02472:Hadhb	APN	5	30,389,061 (GRCm39)	missense	possibly damaging	0.68
R0110:Hadhb	UTSW	5	30,374,483 (GRCm39)	splice site	probably benign
R0578:Hadhb	UTSW	5	30,383,804 (GRCm39)	missense	probably benign
R1483:Hadhb	UTSW	5	30,374,492 (GRCm39)	critical splice acceptor site	probably null
R1552:Hadhb	UTSW	5	30,381,931 (GRCm39)	missense	probably null	0.66
R1616:Hadhb	UTSW	5	30,371,713 (GRCm39)	missense	probably damaging	1.00
R1926:Hadhb	UTSW	5	30,385,935 (GRCm39)	missense	possibly damaging	0.94
R2064:Hadhb	UTSW	5	30,378,796 (GRCm39)	splice site	probably null
R5066:Hadhb	UTSW	5	30,369,094 (GRCm39)	intron	probably benign
R5298:Hadhb	UTSW	5	30,382,009 (GRCm39)	critical splice donor site	probably null
R6216:Hadhb	UTSW	5	30,379,929 (GRCm39)	missense	probably benign	0.00
R6787:Hadhb	UTSW	5	30,360,247 (GRCm39)	unclassified	probably benign
R8480:Hadhb	UTSW	5	30,373,568 (GRCm39)	critical splice donor site	probably null
R8802:Hadhb	UTSW	5	30,378,831 (GRCm39)	nonsense	probably null
R9481:Hadhb	UTSW	5	30,368,711 (GRCm39)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- AGCTGGGACTTGTACACGTTGTC -3'
(R):5'- AAAGCTTGGGGCCACTCAGAAG -3'

Sequencing Primer
(F):5'- GTCTATTTTGTCAGACAGCAAGTTC -3'
(R):5'- tgacatacacctttaatcttgacaac -3'

Posted On

2013-05-23